chr1-15013464-T-C

Position:

• chr1-15013464-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201628.3(KAZN):​c.419-21285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,184 control chromosomes in the GnomAD database, including 55,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (55478 hom., cov: 33)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

Genes affected

KAZN (HGNC:29173): (kazrin, periplakin interacting protein) This gene encodes a protein that plays a role in desmosome assembly, cell adhesion, cytoskeletal organization, and epidermal differentiation. This protein co-localizes with desmoplakin and the cytolinker protein periplakin. In general, this protein localizes to the nucleus, desmosomes, cell membrane, and cortical actin-based structures. Some isoforms of this protein also associate with microtubules. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity has not been verified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN	NM_201628.3	c.419-21285T>C		intron_variant		ENST00000376030.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN	ENST00000376030.7	c.419-21285T>C		intron_variant		5	NM_201628.3	P2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129764 AN: 152064 Hom.: 55436 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.858

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.853 AC: 129864 AN: 152184 Hom.: 55478 Cov.: 33 AF XY: 0.855 AC XY: 63591 AN XY: 74406

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.856

Alfa AF: 0.859 Hom.: 106875

Bravo AF: 0.847

Asia WGS AF: 0.858 AC: 2986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6429703; hg19: chr1-15339960;